As indicated in our previous annual report, an infectivity study of an IG prepared from a plasma pool derived solely from anti-c100-3 reactive donations was initiated in a chimpanzee. The infused IG preparation, designated as HCIG, contained 1709 PCR units (U) of HCV RNA per g of IgG (average value of 495 and 2922 units), and had an anti-HCV titer of 1:1024 when assayed by a multiantigen EIA kit (Ortho). The HCIG was administered intravenously to a chimpanzee at a dosage of 1 g/kg bw, i.e., equivalent to receiving a total of 3 x 104 U of HCV RNA. Since the infusion, the chimpanzee had neither elevated alanine aminotransferase (ALT) (equal to or higher than 2.5 times of the basal value) nor detectable HCV RNA in its weekly serum sample for a period of 50 weeks. Because of the relatively high titer of anti-HCV (present in HCIG) passively transferred to the chimpanzee, anti-HCV in sera was reactive until week 17. To check the susceptibility of the chimpanzee with HCV, it was challenged with 1 ml of a standard HCV inoculum (H plasma, 103.5 CID50) at week 51. HCV RNA was positive since week 53 while ALT was elevated at week 56. Anti-HCV was reactive in sera at weeks 54 and 56 when tested by EIA but was negative when tested by an immunoblot assay (RIBA-2 kit, Chiron). The work is still in progress until the chimpanzee is confirmed to be seroconverted to anti-HCV positive. Nevertheless, based upon the data obtained thus far, the chimpanzee, which was susceptible to HCV infection, was safe when it received a high level of HCV RNA in an IG preparation made entirely from anti-c100-3 reactive donations. We are in the process of obtaining approvals from various committees to use additional chimpanzees for further studies on possible neutralized antibodies present in HCIG.